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Maine Researchers Find Exceptions to Old Rules of Genetic Inheritance

Discoveries by a research team from Maine could help to settle a long-standing debate in genetics.

Some genes are seemingly inseparable in nature; they form a haplotype-a set of genes inherited as a unit. Some researchers support the notion that mapping haplotypes may be more significant than mapping the genome. The haplotype map could allow researchers to look for a single variation in the complex genetic code and know all the variations associated with it, since all are part of the same haplotype.

The Maine research group challenges that proposal, demonstrating that genes within a haplotype function independently. The group included Dr. Antonio Planchart of the Mount Desert Island Biological Laboratory and the College of the Atlantic, Bates College undergraduate Jennifer Reynolds, and Dr. John Schimenti, adjunct senior staff scientist at The Jackson Laboratory.

In feral house mice, 20 percent of the population carries one copy of the t haplotype whereas the remaining 80 percent carries the wild haplotype. According to the distribution predictions set out by Gregor Mendel, the 19th century Austrian monk who studied inheritance in flowering pea plants, males and females should pass the t haplotype to half their offspring.

In a strange twist to what Mendel might have predicted, the males pass the t haplotype to nearly 100 percent of their offspring (a phenomenon known as "transmission ratio distortion")-practically twice the Mendelian prediction.

Stranger still, male and female mice that inherit the t haplotype from both parents typically do not survive, but in the rare instances when they do, the overwhelming majority of males are sterile.

Until now, most geneticists suspected that both transmission ratio distortion and sterility were due to the same mutations in a small number of genes residing in the t haplotype. The hypothesis was logical since the phenomena of transmission ratio distortion and sterility always mappe d to the same regions within the t haplotype.

To test this hypothesis, the Maine researchers closed in on a region of the t haplotype known to be involved in these phenomena. They used this information to develop transgenic mice that carried the candidate region derived from the wild haplotype.

When the transgenic region segregated with the t haplotype, the researchers noted that males carrying two copies of the t haplotype plus the transgenic region were fertile and showed no transmission ratio distortion. Therefore, the scientists realized, two genes must be involved-one controlling sterility and a yet-to-be discovered gene regulating transmission ratio distortion.

Dr. Planchart commented, "For more than 50 years, researchers have sought the biochemical and molecular basis of these phenomena. This work represents a landmark study of the genetics of the t haplotype-it shows for the first time that different genes within the haplotype cause transmission ratio distortion and sterility."

The research is published in the March 1 issue of the Proceedings of the National Academy of Sciences.


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Source:The Jackson Laboratory


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